Podophyllotoxin is a physiologically active substance contained in the aqueous extract of roots and stems of American Mayapple, which is a perennial plant of genus Podophyllum, and podophyllotoxin and derivatives thereof are known to have anticancer activity. However, many of these compounds are poorly water-soluble, and thus research on water-soluble high-molecular weight derivatives of podophyllotoxins and the like has been carried out for the purpose of further improving the effectiveness.
For example, Patent Document 1 describes a high-molecular weight derivative of podophyllotoxins conjugated to polyethylene glycol. However, in these high-molecular weight derivatives of podophyllotoxins, only one to two podophyllotoxin molecules can be bound to one molecule of polyethylene glycol because of its structure, and therefore a large quantities of polymer is required in order to administer an effective amount of the drug.
Patent Document 2 describes a molecule in which a drug is bound to a block copolymer of polyethylene glycol and polyaspartic acid, which forms micelles and has water-solubility. Patent Document 3 describes a polymeric carrier in which a hydrophobic substance is bound to a carboxylic acid group in a side chain of a block copolymer of polyethylene glycol and a poly(acidic amino acid), and which functions as a polymeric drug carrier. Patent Document 4 describes a high-molecular weight derivative of camptothecin in which a carboxylic acid group in a side chain of a block copolymer of polyethylene glycol and polyglutamic acid is bound to a phenolic hydroxyl group of the camptothecins. However, Patent Documents 2 to 4 do not describe about conjugates of podophyllotoxins.
[Patent Document 1] Japanese Patent Application Laid-Open (KOHYO) No. 10-513187
[Patent Document 2] Japanese Patent No. 2694923
[Patent Document 3] Japanese Patent No. 3268913
[Patent Document 4] International Patent Application Publication No. WO 2004/39869 Pamphlet